Effect of ultrasound-guided femoral nerve block with dexmedetomidine and ropivacaine on postoperative analgesia in patients undergoing total knee arthroplasty: a randomized controlled trial.

Background: Dexmedetomidine, a potent and highly selective α2-adrenoreceptor agonist, has become a popular adjuvant to local anesthetics. This study was designed to investigate the effect of dexmedetomidine with ropivacaine for femoral nerve block on postoperative analgesia after total knee arthroplasty. Methods: Forty-six patients after total knee arthroplasty received ultrasound-guided femoral nerve block with either 0.3% ropivacaine alone (group R) or 0.3% ropivacaine with 0.5 µg/kg dexmedetomidine (group RD). Total 24-h sufentanil consumption, visual analogue scale (VAS) pain scores, frequency of patient-controlled analgesia (PCA) pressed, Ramsay sedation score, the incidence of bradycardia and hypotension, and incidence of postoperative nausea and vomiting (PONV) were recorded. Results: Compared to group R, the total 24-h sufentanil consumption was significantly reduced (110.76 ± 11.56 vs. 99.09 ± 13.31; P<0.05), the VAS scores were lower at 10 and 12 h postoperatively [3(2-3) vs. 2(1-2) and 3(2-3) vs. 2(1-3), respectively; P<0.05], the frequency of PCA pressed was lower at 8-12 and 12-16-h time intervals [(5(3-6) vs. 2(1-3) and 4(3-4) vs. 2(1-3), respectively; P<0.05]. However, there were no differences in Ramsay's sedation score and the incidence of PONV. Also, no patient experienced bradycardia and hypotension. Conclusions: 0.5 µg/kg dexmedetomidine with 0.3% ropivacaine for femoral nerve block significantly decreased the total 24-h sufentanil consumption, prolonged and enhanced the analgesic efficacy of ropivacaine, without clinically relevant cardiovascular depression or over-sedation in patients undergoing total knee arthroplasty.

Efficacy and Safety of Different Doses of Remimazolam Tosilate Applied in Upper Gastrointestinal Endoscopy: A Prospective Randomized Controlled Double-Blind Trial.

Background: Remimazolam is a novel benzodiazepine narcotic. When used for gastrointestinal endoscopy or bronchoscopy, it provides adequate sedation and rapid recovery. However, studies on the optimal initial loading dose of remimazolam remain inadequate. Therefore, we conducted a randomized controlled clinical trial to investigate the efficacy and safety of different doses of remimazolam applied in upper gastrointestinal endoscopy. Methods: A total of 218 patients scheduled for upper gastrointestinal endoscopy were included in our trial and divided into experimental and control groups: the experimental groups were the remimazolam groups (R1 of 0.2 mg/kg, R2 of 0.3 mg/kg, and R3 of 0.4 mg/kg), and the control group was the propofol group. Following a single injection of trial drugs during the induction period, operational requirements were evaluated based on MOAA/S scores. When the sedation was successfully achieved, safety was evaluated based on the incidence of various intraoperative and postoperative adverse events. Results: The success rates of intraoperative sedation were 82% in group R1, 98% in group R2, 96% in group R3, and 100% in group P. The incidence of hypotension was lower in the remimazolam groups than in the propofol group (16%), 4% in group R1, 6% in group R2, and 6% in group R3. The incidence of postoperative vertigo was significantly higher, and sedation recovery time was prolonged in high-concentration remimazolam group. Conclusion: Satisfactory efficacy can be obtained with higher concentrations of remimazolam tosilate in patients undergoing upper gastrointestinal endoscopy with ASA grade I or II. However, as the dose is progressively increased, the incidence of adverse reactions by remimazolam tosilate are also significantly increased, such as vertigo and prolonged sedation recovery time. Trial Registration: The trial was registered prior to enrollment at the Chinese Clinical Trial Registry (ChiCTR 2000032067).

Effect of interscalene brachial plexus block with dexmedetomidine and ropivacaine on postoperative analgesia in patients undergoing arthroscopic shoulder surgery: a randomized controlled clinical trial.

BACKGROUND: Dexmedetomidine, a potent and highly selective α2-adrenoreceptor agonist has become a popular adjuvant to local anesthetics. The study was designed to explore the effect of dexmedetomidine added to ropivacaine for interscalene brachial plexus block (IBPB) on postoperative analgesia in patients undergoing arthroscopic shoulder surgery. METHODS: Forty-four adult patients undergoing arthroscopic shoulder surgery were randomly divided into 2 groups. Group R received 0.25% ropivacaine alone, whereas group RD received 0.25% ropivacaine and 0.5 µg/kg dexmedetomidine. A total volume of 15 ml was administered for ultrasound-guided IBPB in both groups. Duration of analgesia, visual analog scale (VAS) pain score, frequency of PCA pressed, first time of PCA pressed, sufentanil consumption, and patient satisfaction with analgesia quality were recorded. RESULTS: Compared with group R, the duration of analgesia was prolonged (8.25±1.76 vs. 11.55±2.41 h; P<0.05), the VAS pain scores were decreased at 8 and 10 h postoperatively (3 (2-3) vs. 0 (0-0) and 2 (2-3) vs. 0 (0-2.25), respectively; P<0.05), the frequencies of PCA pressed were decreased at 4-8 and 8-12 h time intervals (0 (0-0.25) vs. 0 (0-0) and 5 (1.75-6) vs. 0 (0-2), respectively; P<0.05), the time of first PCA pressed was prolonged (9.27±1.85 vs. 12.98±2.35 h; P<0.05), the total 24h sufentanil consumption was reduced (108.72±15.92 vs. 94.65±12.47 µg; P<0.05 ) and patient satisfaction score was also improved (3 (3-4) vs. 4 (4-5); P<0.05) in group RD. CONCLUSION: We concluded that adding 0.5 µg/kg dexmedetomidine to 0.25% ropivacaine for IBPB provided better postoperative analgesia, decreased the sufentanil consumption and improved the patient's satisfaction in patients undergoing arthroscopic shoulder surgery.

Carbon Nanostructures for Ocular Tissue Reinforcement.

Purpose: The purpose of this study was to improve the biomechanical properties of the cornea through the incorporation of carbon nanostructures. Methods: Healthy Japanese rabbits were used to evaluate the effect of carbon nanostructures' incorporation in the cornea. Rabbits were divided in two groups A and B. In each of these groups, the corneas were divided in (i) corneas not submitted to any treatment (the control group), (ii) corneas modified either with carbon nanostructures (group A), or with the traditional cross-linking technology (group B). After modification, rabbits were euthanized at different time intervals. The biomechanical properties of the treated corneas were evaluated using the inflation method. Results: Biomechanical tests based on the inflation method show that the incorporation of carbon nanostructures to the cornea and their proper distribution within it gives rise to a large improvement in the mechanical properties and tangential elastic modulus (up to 155%). These results anticipate that this novel and easy approach based on nanotechnology is able to compete with the actual cross-linking technology applied in clinical ophthalmology using a photosensitive molecule, such as riboflavin and unpleasant UV-A radiation. Conclusions: The incorporation of carbon nanostructures (single-walled carbon nanotubes and graphene) in corneal stroma is proposed as a promising alternative to improve the mechanical properties in the treated eyes. The proper dispersion of the carbon nanostructures a few days after implementation (down to 60 micrometers depth) explains the successful results achieved. Translational Relevance: Nanotechnology applied to the eye constitutes a promising approach for ocular tissue reinforcement.

Serum Soluble ST2 Correlated with Symptom Severity and Clinical Response of Sublingual Immunotherapy for House Dust Mite-Induced Allergic Rhinitis Patients.

BACKGROUND: Suppressor of tumorigenicity 2 (ST2) is a key biomarker in inflammation and cardiovascular diseases, but limited data is available on its role in allergic rhinitis (AR). OBJECTIVE: The aim of this study is to explore the role of serum soluble ST2 (sST2) in evaluating disease severity and predicting the efficacy of sublingual immunotherapy (SLIT) in house dust mite- (HDM-) induced AR patients. METHODS: Eighty healthy controls (HC group) and 160 HDM-induced AR patients, including 40 mild patients (MAR group) and 120 moderate-severe patients (MSAR group), were recruited in this study. Serum was collected from all participants and levels of sST2 were determined by ELISA and the relationship between sST2 levels and disease severity was assessed. In the MSAR group, 109 patients received 3 years of SLIT, and the relationship between serum levels of sST2 and efficacy of SLIT was exampled. RESULTS: Serum sST2 levels were increased in HDM-induced AR patients compared to the HC group (P < 0.001), and the concentrations were higher in the MSAR group than in the MAR group and HC group (all P < 0.05). Moreover, sST2 levels positively correlated with the total nasal symptom score (TNSS), visual analogue scale (VAS), and specific IgE levels (P < 0.05). Seventy-eight MSAR patients accomplished SLIT, and they were divided into an effective group (n = 40) and an ineffective group (n = 38). The serum sST2 levels in the effective group were lower than those in the ineffective group (P < 0.001). In addition, patients in the effective group levels exhibited significantly lower sST2 levels post-SLIT than pre-SLIT (P < 0.001), but no statistic difference was observed in the ineffective group (P > 0.05). Receiver operating characteristic (ROC) curve showed promising accuracy for predicting clinical efficacy of SLIT in AR patients (area under the curve = 0.839, P < 0.001). CONCLUSION: Serum sST2 is a potential biomarker for assessing disease severity and may serve as a sensitive biomarker for predicting the therapeutic response of SLIT in HDM-induced AR patients.

Long Noncoding RNA THAP9-AS1 and TSPOAP1-AS1 Provide Potential Diagnostic Signatures for Pediatric Septic Shock.

BACKGROUND: Sepsis is a systemic inflammatory syndrome caused by infection with a high incidence and mortality. Although long noncoding RNAs have been identified to be closely involved in many inflammatory diseases, little is known about the role of lncRNAs in pediatric septic shock. METHODS: We downloaded the mRNA profiles GSE13904 and GSE4607, of which GSE13904 includes 106 blood samples of pediatric patients with septic shock and 18 health control samples; GSE4607 includes 69 blood samples of pediatric patients with septic shock and 15 health control samples. The differentially expressed lncRNAs were identified through the limma R package; meanwhile, GO terms and KEGG pathway enrichment analysis was performed via the clusterProfiler R package. The protein-protein interaction (PPI) network was constructed based on the STRING database using the targets of differently expressed lncRNAs. The MCODE plug-in of Cytoscape was used to screen significant clustering modules composed of key genes. Finally, stepwise regression analysis was performed to screen the optimal lncRNAs and construct the logistic regression model, and the ROC curve was applied to evaluate the accuracy of the model. RESULTS: A total of 13 lncRNAs which simultaneously exhibited significant differences in the septic shock group compared with the control group from two sets were identified. According to the 18 targets of differentially expressed lncRNAs, we identified some inflammatory and immune response-related pathways. In addition, several target mRNAs were predicted to be potentially involved in the occurrence of septic shock. The logistic regression model constructed based on two optimal lncRNAs THAP9-AS1 and TSPOAP1-AS1 could efficiently separate samples with septic shock from normal controls. CONCLUSION: In summary, a predictive model based on the lncRNAs THAP9-AS1 and TSPOAP1-AS1 provided novel lightings on diagnostic research of septic shock.

A randomized controlled trial for measuring effects on cognitive functions of adding ketamine to propofol during sedation for colonoscopy.

BACKGROUND: The purpose of this study was to evaluate the effects of adding ketamine to propofol on cognitive functions in patients undergoing sedation for colonoscopy. METHODS: In this randomized, double-blinded, and controlled study, 200 patients were randomly allocated to ketamine/propofol admixture group (Group KP, n = 100), and propofol group (Group P, n = 100). Patients in Group KP received 0.25 mg/kg of ketamine and 0.5 mg/kg of propofol. Patients in Group P received 0.5 mg/kg propofol. Cognitive functions were measured using CogState battery before and after the colonoscopy procedure. Ninety five patients in Group KP and 92 patients in Group P had completed the CogStates tests and were included in the data analysis. RESULTS: Compared with before procedure baseline, the performance on detection and identification tasks were significantly impaired after the procedure in both Group KP (P = .004, P = .001) and Group P patients (P = .005, P < .001). However, one-card learning accuracy and One-back memory was only impaired in Group KP patients (P = .006, P = .040) after the endoscopy but left intact in Group P patients. Group KP patients showed more severe impairment in one-card learning accuracy compared with Group P patients (P = .044). Group KP patients have better 5 minutes MAP (P = .005) and were also less likely to suffer from complications such as respiratory depression (P = .023) and hypotension (P = .015). OAA/S scores, BIS, MAP, complications, recovery times, and endoscopist and patient satisfaction were similar between the 2 groups. CONCLUSION: Although adding ketamine to propofol for sedation in colonoscopy provided fewer complications such as respiratory depression and hypotension, it also causes more impairment in cognitive functions.

Ultrasound-guided transversus abdominis plane block using ropivacaine and dexmedetomidine in patients undergoing caesarian sections to relieve post-operative analgesia: A randomized controlled clinical trial.

Dexmedetomidine, which is a highly selective α2 adrenoreceptor agonist, enhances the analgesic efficacy and prolongs the analgesic duration when administered in combination with local anesthetics. The current study aimed to evaluate the effects of dexmedetomidine combined with ropivacaine in ultrasound-guided transversus abdominis plane (TAP) block on post-operative analgesia following cesarean section (CS). A total of 70 patients scheduled for CS were divided randomly into 2 groups: The ropivacaine (R) group, in which patients were administered bilateral 20 ml 0.3% ropivacaine and 2 ml 0.9% normal saline, and the dexmedetomidine (RD) group, in which patients were administered bilateral 20 ml 0.3% ropivacaine and 2 ml dexmedetomidine (0.5 µg/kg). The primary outcome was pain-free duration, and secondary outcomes included heart rate (HR) and mean blood pressure (MBP) measurements, visual analogue scale (VAS) pain scores, number of patients who required rescue analgesic, time to first request for analgesia and patient satisfaction. There was no significant difference in HR and MBP between the two groups at 1 h post-surgery (P>0.05). However, VAS pain scores decreased at 6 and 8 h post-surgery [2 (1-2) vs. 0 (0-0.25) and 2 (2-3) vs. 0 (0-1), respectively; P<0.05], pain-free duration was prolonged (5.91±1.08 vs. 9.62±1.46 h; P<0.05), the number of patients who required rescue analgesic was reduced (19 vs. 9; P<0.05), the time to first request for analgesia was prolonged (7.10±1.21 vs. 11.60±2.11 h; P<0.05) and patient satisfaction was improved [3.5 (3-4) vs. 4 (4-5); P<0.05] in the RD group compared with the R group. Furthermore, no bradycardia or hypotension was observed. In conclusion, the results of the present study demonstrated that adding 0.5 µg/kg dexmedetomidine to 0.3% ropivacaine used in TAP block in patients undergoing CS prolonged pain-free duration, decreased VAS pain scores, reduced the number of patients who required rescue analgesic, prolonged the time to first request for analgesia and improved the patient satisfaction without serious side effects.

Transesophageal Echocardiographic Measurements of the Superior Vena Cava for Predicting Fluid Responsiveness in Patients Undergoing Invasive Positive Pressure Ventilation.

OBJECTIVES: Preoperative fasting, water deprivation, and intraoperative fluid loss and redistribution result in hypovolemia in patients undergoing surgery. Some findings have indicated that the superior vena cava (SVC) diameter and variation, as determined by transesophageal echocardiography during surgery, do not reflect central venous pressure effectively. This study aimed to compare and correlate the SVC diameter and variation with the stroke volume variation for predicting fluid responsiveness in patients undergoing invasive positive pressure ventilation. METHODS: Thirty-six patients scheduled for elective gastrointestinal surgery under general anesthesia with invasive positive pressure ventilation were included in this study. After anesthesia induction, the stroke volume variation, SVC diameter, mean arterial pressure, central venous pressure, and pulse were recorded, and measurements after fluid challenge were recorded as well. The SVC variation was calculated before and after the fluid challenge. RESULTS: After the fluid challenge, the SVC diameter markedly increased, whereas the SVC variation and stroke volume variation significantly decreased (P < .05). The optimal cutoff value for the SVC variation was 21.1%, and the area under the curve (AUC) from a receiver operating characteristic curve analysis was 0.849. The optimal cutoff value for the minimal SVC diameter was 1.135 cm, and that AUC was 0.929. In addition, the optimal cutoff value for the maximal SVC diameter was 1.480 cm, and the AUC was 0.862. CONCLUSIONS: The minimal SVC diameter may be an effective indicator for predicting fluid responsiveness in patients undergoing invasive positive pressure ventilation.

Effect of dexmedetomidine added to ropivicaine for caudal anesthesia in patients undergoing hemorrhoidectomy: A prospective randomized controlled trial.

BACKGROUND: To assess the effect of dexmedetomidine added to ropivaccaine on the onset and duration of sensory block, as well as postoperative analgesia during caudal anesthesia in patients undergoing hemorrhoidectomy. METHODS: Fifty adult patients scheduled for hemorrhoidectomy were divided into 2 groups. The group R received caudal anesthesia using 18 mL 0.3% ropivacaine plus 2 mL normal saline. The group RD received 18 mL 0.3% ropivacaine plus 2 mL 1 µg/kg dexmedetomidine. Heart rate, mean blood pressure, onset time and duration of sensory block, and duration of analgesia were observed. RESULTS: The onset time of sensory block was shortened (9.2 ±â€Š1.3 vs 7.2 ±â€Š1.2), and the duration of sensory block (3.0 ±â€Š0.7 vs 3.8 ±â€Š0.8) and duration of analgesia (3.9 ±â€Š0.7 vs 5.3 ±â€Š0.8) were prolonged in group RD compared with group R (P < .05). The heart rate and the mean blood pressure were also lower in the group RD compared with group R at each observation time points, except the baseline (P < .05). No bradycardia or hypotension was reported. CONCLUSION: Dexmedetomidine as an adjuvant to ropivacaine prolonged the duration of caudal block and improved postoperative analgesia without significant side effects in adult patients undergoing hemorrhoidectomy.

Proteomic insight into fruit set of cucumber (Cucumis sativus L.) suggests the cues of hormone-independent parthenocarpy.

BACKGROUND: Parthenocarpy is an excellent agronomic trait that enables crops to set fruit in the absence of pollination and fertilization, and therefore to produce seedless fruit. Although parthenocarpy is widely recognized as a hormone-dependent process, hormone-insensitive parthenocarpy can also be observed in cucumber; however, its mechanism is poorly understood. To improve the global understanding of parthenocarpy and address the hormone-insensitive parthenocarpy shown in cucumber, we conducted a physiological and proteomic analysis of differently developed fruits. RESULTS: Physiological analysis indicated that the natural hormone-insensitive parthenocarpy of 'EC1' has broad hormone-inhibitor resistance, and the endogenous hormones in the natural parthenocarpy (NP) fruits were stable and relatively lower than those of the non-parthenocarpic cultivar '8419 s-1.' Based on the iTRAQ technique, 683 fruit developmental proteins were identified from NP, cytokinin-induced parthenocarpic (CP), pollinated and unpollinated fruits. Gene Ontology (GO) analysis showed that proteins detected from both set and aborted fruits were involved in similar biological processes, such as cell growth, the cell cycle, cell death and communication. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that 'protein synthesis' was the major biological process that differed between fruit set and fruit abortion. Clustering analysis revealed that different protein expression patterns were involved in CP and NP fruits. Forty-one parthenocarpy-specialized DEPs (differentially expressed proteins) were screened and divided into two distinctive groups: NP-specialized proteins and CP-specialized proteins. Furthermore, qRT-PCR and western blot analysis indicated that NP-specialized proteins showed hormone- or hormone-inhibitor insensitive expression patterns in both ovaries and seedlings. CONCLUSIONS: In this study, the global molecular regulation of fruit development in cucumber was revealed at the protein level. Physiological and proteomic comparisons indicated the presence of hormone-independent parthenocarpy and suppression of fruit abortion in cucumber. The proteomic analysis suggested that hormone-independent parthenocarpy is regulated by hormone-insensitive proteins such as the NP-specialized proteins. Moreover, the regulation of fruit abortion suppression may be closely related to protein synthesis pathways.

Effect of dexmedetomidine as an adjuvant to ropivacaine for wound infiltration in patients undergoing open gastrectomy: A prospective randomized controlled trial.

OBJECTIVES: The primary objective of this study was to investigate whether dexmedetomidine could potentiate the analgesic efficacy of ropivacaine, when added to ropivacaine for wound infiltration in patients undergoing open gastrectomy. METHODS: Fifty patients scheduled for open gastrectomy were divided into 2 equal groups that were received wound infiltration using 20 mL 0.3% ropivacaine plus 2 mL normal saline (group R) or 20 mL 0.3% ropivacaine plus 2 mL 1.0 µg/kg dexmedetomidine (group DR). Visual analogue scale (VAS) pain score, patient-controlled analgesia (PCA) pump press number, sufentanil consumption, postoperative nausea and vomiting (PONV), and wound healing score were recorded. RESULTS: The VAS pain score were comparable between the 2 groups at the observation time points (P > .05), PCA pump press number and sufentanil consumption were higher in group R than that in group DR at 0 to 2, 2 to 4, 4 to 6 time intervals (P < .05) except for 6 to 8, 8 to 10, 10 to 12 time intervals (P > .05), meanwhile, the 24 hours total sufentanil consumption was also higher in group R than that in group DR (90.4 ±â€Š20.5 vs 79.2 ±â€Š9.4) (P < .05), there were no significant differences in PONV and wound healing score between the 2 groups (P > .05). CONCLUSIONS: Dexmedetomidine as an adjuvant to ropivacaine for wound infiltration promoted the analgesic efficacy of ropivacaine, reduced sufentanil consumption, and had no effect on wound healing; it could be as an ideal adjuvant which could potentiate the analgesic efficacy of local anesthetics.

New insights into the roles of cucumber TIR1 homologs and miR393 in regulating fruit/seed set development and leaf morphogenesis.

BACKGROUND: TIR1-like proteins act as auxin receptors and play essential roles in auxin-mediated plant development processes. The number of auxin receptor family members varies among species. While the functions of auxin receptor genes have been widely studied in Arabidopsis, the distinct functions of cucumber (Cucumis sativus L.) auxin receptors remains poorly understood. To further our understanding of their potential role in cucumber development, two TIR1-like genes were identified and designated CsTIR1 and CsAFB2. In the present study, tomato (Sonanum lycopersicum) was used as a model to investigate the phenotypic and molecular changes associated with the overexpression of CsTIR1 and CsAFB2. RESULTS: Differences in the subcellular localizations of CsTIR1 and CsAFB2 were identified and both genes were actively expressed in leaf, female flower and young fruit tissues of cucumber. Moreover, CsTIR1- and CsAFB2-overexpressing lines exhibited pleotropic phenotypes ranging from leaf abnormalities to seed germination and parthenocarpic fruit compared with the wild-type plants. To further elucidate the regulation of CsTIR1 and CsAFB2, the role of the miR393/TIR1 module in regulating cucumber fruit set were investigated. Activation of miR393-mediated mRNA cleavage of CsTIR1 and CsAFB2 was revealed by qPCR and semi-qPCR, which highlighted the critical role of the miR393/TIR1 module in mediating fruit set development in cucumber. CONCLUSION: Our results provide new insights into the involvement of CsTIR1 and CsAFB2 in regulating various phenotype alterations, and suggest that post-transcriptional regulation of CsTIR1 and CsAFB2 mediated by miR393 is essential for cucumber fruit set initiation. Collectively, these results further clarify the roles of cucumber TIR1 homologs and miR393 in regulating fruit/seed set development and leaf morphogenesis.

Effect of Repetitive Intracutaneous Injections with Local Anesthetics and Steroids for Acute Thoracic Herpes Zoster and Incidence of Postherpetic Neuralgia.

BACKGROUND: Treatment of established postherpetic neuralgia (PHN) is difficult and often disappointing. In this study, we assessed the efficacy of repetitive intracutaneous injections with local anesthetics and steroids in acute thoracic herpes zoster (HZ) pain, herpetic eruption, and incidence of PHN. METHODS: Ninety-three patients with acute thoracic HZ were randomly assigned to receive a standard treatment of antiviral medication with p.o. analgesics or the standard treatment with the addition of repetitive intracutaneous injections of a local anesthetic and steroid mixture. Patients were permitted to take tramadol when the visual analog scale (VAS) ≥ 4. Pain assessment using VAS was conducted at the initial visit, as well as 1, 2, 4, 12, and 24 weeks after the end of the treatments. RESULTS: In comparison with the standard treatment group, the VAS scores of the intracutaneous injection group were significantly lower during the study. The intracutaneous injection group also reported shorter duration of pain and skin eruption than the control group ( P = 0.005 vs P < 0.001, respectively). At 1 month post-therapy, 12.8% patients in the intracutaneous injection group reported zoster-associated pain, compared with 47.8% in the standard treatment group ( P < 0.001). At 3 and 6 months post-therapy, the incidence of PHN was still significantly lower in the intracutaneous injection group than the standard treatment group. EuroQol VAS scores were significantly higher in the intracutaneous injection group vs standard treatment group (P < 0.001). CONCLUSION: Repetitive intracutaneous injections with local anesthetics and steroids along with standard treatment significantly reduce the duration of pain and herpetic eruption and incidence of PHN.

Prospective association of a genetic risk score with major adverse cardiovascular events in patients with coronary artery disease.

Many susceptibility loci associated with coronary artery disease (CAD) have been identified using genome-wide association studies (GWAS). This study aimed to examine whether a composite of single nucleotide polymorphisms (SNPs) derived from GWAS could identify the risk of major adverse cardiovascular events (MACEs) in patients with established CAD. There were 1059 patients with CAD were included in the analysis. Of the participants, 686 were on statin treatment at the start of follow-up. A weighted genetic risk score (wGRS) was calculated as the sum of risk alleles multiplied by the hazard ratio for a particular SNP. In single variant analyses, rs579459, rs4420638, and rs2107595 were associated with an increased risk of MACE. A wGRS was further constructed to evaluate the cumulative effect of the 3 SNPs on the prognosis of CAD. The risk of MACE among patients with high and intermediate wGRS was 1.968- and 1.838-fold, respectively, higher than those with low wGRS. This effect was more evident in patients using lipid-lowering medication and with hypertension. Furthermore, the interaction analysis revealed that lipid-lowering medication and hypertension interacted with the genetic effect off wGRS on the risk of MACE in patients using lipid-lowering medication or with hypertension (Pinteraction < .001). We further analyzed the follow-up change in low-density lipoprotein cholesterol (LDL-C) level at 6 months after CAD disclosure and evaluated whether that was due to wGRS or statin use. The lowest reduction in LDL-C was observed in patients with high GRS who received statin treatment. Furthermore, LDL-C reduction of patients with intermediate wGRS was less than those with low wGRS in patients treated with statin. Taken together, a wGRS comprised of SNPs significantly predicts MACE in CAD patients receiving statin treatment and hypertension.

Ultrasonographic measurements of the inferior vena cava variation as a predictor of fluid responsiveness in patients undergoing anesthesia for surgery.

BACKGROUND: Both hypovolemia and hypervolemia are connected with increased morbidity and mortality in the treatment and prognosis of patients. An accurate assessment of volume state allows the optimization of organ perfusion and oxygen supply. Recently, ultrasonography has been used to detect hypovolemia in critically ill patients and perioperative patients. The objective of our study was to assess the correlation between inferior vena cava (IVC) variation obtained with ultrasound and stroke volume variation (SVV) measured by the Vigileo/FloTrac monitor, as fluid responsiveness indicators, in patients undergoing anesthesia for surgery. METHODS: Forty patients (American Society of Anesthesiologists grades I and II) scheduled for elective gastrointestinal surgery were enrolled in our study. After anesthesia induction, 6% hydroxyethyl starch solution was administered to patients as an intravenous (IV) fluid. The IVC diameters were measured with ultrasonography. SVV and stroke volume index (SVI) were obtained from the Vigileo monitor. All data were collected both before and after fluid challenge. RESULTS: Forty patients underwent IVC sonographic measurements and SVV calculation. After fluid challenge, mean arterial pressure, central venous pressure, SVI, and IVC diameters increased significantly, whereas SVV decreased markedly. The correlation coefficient between the increase in SVI and the baseline of IVC variation after an IV fluid was 0.710, and receiver operating characteristic (ROC) curve was 0.85. The correlation coefficient between the increase in SVI and the baseline of SVV was 0.803 with an ROC curve of 0.93. Central venous pressure had no significant correlation with SVI. CONCLUSIONS: Our data show that IVC variation and SVV proved to be reliable predictors of fluid responsiveness in patients undergoing anesthesia for surgery with mechanical ventilation.

Effect of dexmedetomidine added to ropivacaine on ultrasound-guided transversus abdominis plane block for postoperative analgesia after abdominal hysterectomy surgery: a prospective randomized controlled trial.

BACKGROUND: To identify the effect of dexmedetomidine added to ropivacaine on ultrasound-guided transversus abdominis plane block for postoperative analgesia after abdominal hysterectomy surgery. METHODS: Sixty patients were enrolled in the study and divided into two groups. Bilateral 20 mL 0.3% ropivacaine and 2 mL 0.9% normal saline for ropivacaine group (group R), and bilateral 20 mL 0.3% ropivacaine and 2 mL dexmedetomidine (0.5 µg/kg) for dexmedetomidine group (group RD). Visual Analogue Scale (VAS) pain scores, frequency of PCA pressed, sufentanil consumption, and postoperative nausea and vomiting (PONV) were recorded. RESULTS: There was no significant difference in VAS pain scores between the two groups at different time intervals (P>0.05). Compared with group RD, the frequency of PCA pressed and integrated consumption of sufentanil were significantly higher in Group R at 0-2, 2-4, 4-6, 6-8, time intervals (P<0.05) except for 8-12,12-24 time intervals (P>0.05), and the 24h total sufentanil consumption and frequency of PCA pressed were also higher in group R (63.9±10.0 vs. 51.8±9.1, 8.3±1.7 vs. 5.4±1.6) (P<0.05). There was no difference in PONV between the two groups (P>0.05). CONCLUSIONS: Ultrasound-guided TAP block could be as an effective component of multimodal postoperative analgesic regimen; adding dexmedetomidine to ropivacaine in TAP block potentiated the analgesic properties of ropivacaine, reduced sufentanil consumption and provided better pain control after abdominal hysterectomy surgery.

Manipulating the Hippo-Yap signal cascade in stem cells for heart regeneration.

The Hippo-Yap pathway was originally recognized as a crucial signal cascade controlling organ size, and more recently identified as an important component involved in the regulation of cardiomyocyte survival, proliferation, and regeneration. Negative stress responses can activate mammalian sterile 20-like kinase 1 (Mst1) to suppress protective autophagy and promote cardiomyocyte apoptosis via phosphorylation and inhibition of Bcl-xL. Moreover, decreased Yap activity and nuclear entry will decrease upon Mst1 activation, ultimately suppressing cardiomyocytes proliferation and regeneration. Based on these observations, there are potential therapeutic opportunities in cardiac structural and functional regeneration post myocardium infarction to be gained by manipulation of the Hippo-Yap signal cascade. This review will summarize the main components of the Hippo-Yap pathway and their molecular biological functions. It will then highlight the role of these signal modules in the acquisition of stem cell pluripotency, cardiogenic differentiation, cardiomyocyte proliferation and maturation, and mitochondrial biogenesis in cardiac stem cells. Finally, it will discuss the potential for future studies of Hippo-Yap pathway using induced pluripotent stem cell (iPSC) technology.

Role of the mevalonate pathway in specific CpG site demethylation on AGEs-induced MMP9 expression and activation in keratinocytes.

BACKGROUND: Advanced glycation end products (AGEs) played an important role for the development of diabetic foot. In the present study we tried to show the mevalonate pathway and the key demethylation site(s) in the MMP-9 cis-promoter to the component of MMP-9 by AGEs in keratinocyte. METHOD: Human keratinocyte cell line (HaCaT) cells were exposed to AGE-BSA. The plasmid construction and site-directed mutagenesis, dual-luciferase reporter assays, immunoblot, zymography, pull down, bisulfite sequencing PCR analysis and Western blotting were applied. RESULTS: The AGE-BSA could increase and more activate the MMP9 in keratinocyte. The RhoA and ROCK1 also could be activated. These affects were blocked by the simvastatin. Meanwhile, the CpG site at -562 site was largely demethylated with AGE-BSA treatment. The cis-promoter sequences with -562 bp site methylated had a lower activity change, which had a highest expression activity and was decreased by simvastatin. Moreover, site-directed mutagenesis of CpG site (-562 bp) in the recombinant plasmid pCpGL-571 brought more reduction in activity, and the activity of methylated mutation pCpGL-571 remains decreased. CONCLUSION: The cis-promoter regions of MMP9 would be methylated by AGE-BSA in keratinocyte through the mevalonate pathway, especially the -562 bp site.